Diaper rash is a common form of irritation and inflammation of those parts of an infant's body normally covered by a diaper. It frequently occurs also in areas immediately adjacent to the diapered area. This condition is also referred to as diaper dermatitis, napkin dermatitis, napkin rash, and nappy rash.
The precise number of infants who suffer from diaper rash or diaper dermatitis is unknown. However, the United States Department of Health, Education and Welfare, has indicated that diaper dermatitis itself accounted for 97 visits to a doctor for every 1,000 infants in the United States between the ages of 0 to 2 years of age. See Ambulatory Care Utilization Patterns of Children and Young Adults, Vital and Health Statistics Series 13, Number 39, U.S. Department of Health, Education and Welfare, Public Health Service (1978). Further, while certainly more common in infants, this condition is not, in fact, limited to infants. Any individual who suffers from incontinence may develop this condition. This ranges from newborns, to the elderly, to critically ill or nonambulatory individuals.
It is generally accepted that true "diaper rash" or "diaper dermatitis" is a condition which is, in its most simple stages, a contact irritant dermatitis. See Jacobs, "Eruptions in the Diaper Area", Pediatr Clin North Am 25:209 (1978). The irritation of simple diaper rash results from extended contact of the skin with urine, or feces, or both. Diapers are worn to catch and hold the body waste, but generally holds the waste in direct contact with the skin until changed, i.e., in occluded fashion for long periods of time. The same is true for an incontinence pad, or incontinence brief. However, while it is known that body waste "causes" diaper rash, the precise component or components of the urine or feces which are responsible for the resulting irritation of the skin remain the subject of much controversy. The most commonly accepted list of factors linked to diaper rash includes ammonia, bacteria, the products of bacteria action, urine pH, Candida albicans, and moisture. These are generally cited in the art as being the most likely candidates. No conclusive investigations have been reported to date.
There are a host of conditions which are labeled (or more precisely mislabeled) "diaper rash" which may exhibit similar indications. In determining whether the condition that is being observed is actually diaper rash/dermatitis or some other condition no conclusive rule exists. If the dermatitis is limited to the diapered area and related to the use of the diaper or the contact of skin to body waste it can be safely concluded that the condition that exists is diaper dermatitis. There are a number of other conditions, however, which can begin in the area that is diapered on the infant, or which are simply more pronounced or aggravated in this area, but which are not truly "diaper rash" or "diaper dermatitis" in that they are not related to body waste contact. If the abnormal skin condition under scrutiny is present in locations other than in, or proximate to, the diapered area, e.g., the head, neck, extremities other than the genitalia, shoulders, etc., then one must consider other conditions, such as atopic dermatitis, seborrheic dermatitis, allergic contact dermatitis, psoriasis, scabies, bullous impetigo, papular urticaria, herpes simplex, and chemical or thermal burns. However, such observations are not conclusive because some diaper rash or diaper dermatitis conditions may have their genesis in the diapered area and then spread well beyond the diapered area.
This invention, and the accompanying discussion, deals only with compositions and methods for the treatment of diaper rash or diaper dermatitis, and other conditions which are associated with prolonged contact of the skin with urine, feces, or urine-feces mixtures, and/or the wearing of a diaper.
Weston, et al., "Diaper Dermatitis: Current Concepts", Pediatrics 66:4 (1980) has described and summarized the overall clinical features which can generally be associated with true diaper dermatitis. He has identified the forms of diaper rash or diaper dermatitis as follows:
Four clinical forms of diaper dermatitis felt to be related to diaper wear have been recognized. The most frequently observed is chafing dermatitis. This form demonstrates mild redness and scaliness seen over the buttocks, waist, and convex surface of the thighs where the diaper contacts the skin, or limited to the perianal area. Dermatitis limited to the perianal area is seen in the neonatal period, and the more widespread form is seen after 3 months of age. The second, and also frequently seen, form of dermatitis is a sharply demarcated confluent erythema with involvement of the skin folds with or without an accompanying whitish exudate. The third form of dermatitis is characterized by discrete shallow ulcerations scattered throughout the diaper area including the genitalia. In the fourth form, beefy red confluent erythema of the entire perineum with prominent elevated margins, satellite oval lesions around the periphery of the confluent area, and vesiculopustular lesions are described. This form is seen when the dermatitis becomes secondarily invaded with Candida albicans. Diffuse involvement of the genitalia in the inguinal folds is a regular feature of this form.
Thus, it is clear that diaper rash and diaper dermatitis may be merely a general inconvenience to the child, and, in turn, the parent. If left untreated, diaper rash and diaper dermatitis can result in masceration of the skin, thus leading to much more serious conditions and pathologies, e.g., infection, trauma, and systemic disease. See Burgoon, "Diaper Dermatitis", Pediatric Clinics of North America 18:835 (1961).
While no true causative agent has been identified, a diverse range of factors have been suspected of being associated with diaper rash and diaper dermatitis. Because these suspected agents all possess diverse properties and require such varied therapies, conventional methods of treatment for diaper dermatitis have been directed toward a straightforward attempt to minimize the contact of the skin with the feces or urine present in a soiled diaper. An artificial barrier is usually provided between the skin and the body waste to accomplish this. There have also been further attempts directed toward counteracting other suspected causes of diaper rash by promoting dryness in the diapered area, and preventing microbial growth and inflammation with conventional agents. Such a strategy would include frequent diaper changing, reduced use of plastic pants, triple diapering, careful washing and sterilization of diapers, treatment with an anti-Candidal agent, reduction of inflammation (by application of a topical application of a low potency glucocorticoid steroid), and the possible use of a bacteriostatic agent as a prophylactic measure in the diaper rinse. However, because the exact components of urine or feces which act as factors or cofactors contributing to diaper dermatitis have never been precisely identified, the most effective method of treating diaper dermatitis to date has been the artificial barrier. This had led to the frequent use of an occlusive, barrier-type topical, such as petrolatum or zinc oxide, to provide this protection, preventing the unknown offending component from coming in contact with the skin.
For example, Desitin.RTM. ointment, (Leeming Division of Pfizer, Inc.) is probably the most common topical used in treating diaper rash. It contains both of the common barrier materials (zinc oxide and petrolatum) and additionally contains two common skin conditioning agents (cod liver oil and lanolin). All of these agents are commonly used in topical skin conditioning preparations.
Petrolatums, as well as zinc oxide, are well known to be highly effective barrier materials.
Zinc oxide is also known to be effective when applied externally--as a mild astringent for the skin, as a barrier material to prevent eczema, and also as a barrier protective to slight excoriations. It has been used in pastes and cremes in combination with many other topical actives. See Martindale, The Extra Pharmacopoeia, 26th Ed., p. 585, The Pharmaceutical Press (1975). Zinc oxide is almost totally insoluble in water.
Petrolatum (petroleum jelly; paraffin jelly; vasoliment; Vaseline) is commonly used as an occlusive barrier material in topical preparations. Petrolatum is a purified mixture of semi-solid hydrocarbons of the general formula C.sub.n H.sub.2n+2, when n is about 16 to about 32. Premium petrolatum is a white, semi-solid, unctious mass which is odorless and tasteless. It is a product of commerce.
Zinc glycerolate (the reaction product of zinc oxide and glycerine) is cited as being useful as a topical treatment for skin disorders, including ammoniacal dermatitis in babies in Patent Cooperation Treaty Application 8201-867. This disclosure indicates that the "zinc glycerolate" complex is insoluble in water. CuCl.sub.2 is disclosed as a dye useful in this product. See, Patent Cooperation Treaty Application 8201-867, Taylor, filed Nov. 8, 1981, published June 10, 1982.
Zinc chloride is known as a powerful caustic and astringent. Its known uses include incorporation within mouthwashes, eye drops, and as deodorizer for foul smelling wounds and ulcers. See Martindale, The Extra Pharmacopoeia, 26th Ed., p. 270, The Pharmaceutical Press (1975).
U.S. Pat. No. 4,349,536, Hausler, issued Sept. 14, 1982, describes the use of zinc(II) and copper(II) trace minerals in a cream base to promote suntanning.
U.S. Pat. No. 4,160,820, Sipos, issued July 10, 1979, indicates that a glycerine solution containing about 0.5% to about 8% of a glycerine-soluble zinc salt is useful in the treatment of gingivitis when applied topically to the gums.
U.S. Pat. No. 3,996,346, Staffier, et al., issued Dec. 7, 1976, indicates that a combination of zinc oxide and zinc phenate (Zn)(C.sub.6 H.sub.5 OH).sub.2 is useful as a deodorant and an anti-perspirant when applied topically to the underarm area or the feet.
U.S. Pat. No. 3,964,486, Blaney, issued June 22, 1976, describes a disposable diaper or pad comprising an absorbent substrate having incorporated therein adipic acid in a quantity sufficient to inhibit ammonia formation and concommitant diaper rash. It describes the use of adipic acid in the diaper at a level sufficient to provide the urine with a pH in the range of about 3.5 to about 5.5 during use throughout the entire diaper upon wetting with urine.
A CuSO.sub.4 /ZnSO.sub.4 combination is useful as a wet dressing in the treatment of eczema and impetigo in addition to being useful as a local astringent for eye infections. Martindale, The Extra Pharmacopoeia, 26th Ed., p. 475, The Pharmaceutical Press (1975).
Soluble metallic salts, particularly zinc, silver and lead ions, are known as lipase inhibitors. See Lowenstein, Methods in Enzymology, Vol. XIV, p. 176, Academic Press, (1969).
It is also known that the salts of copper are useful in topicals, astringents and fungicides. Martindale, The Extra Pharmacopoeia, 26th Ed., p. 473-475, The Pharmaceutical Press, (1975).
Polyethylene glycols (PEG's) are polymers produced by the reaction of ethylene oxide with ethylene glycol or water. PEG's with molecular weights up to about 600 are liquids at room temperature and they closely resemble highly-refined petrolatum/mineral oils in appearance and consistency. They are widely used as ointment bases for water-soluble agents. Goodman, et al., The Pharmacological Basis of Therapeutics, 5th Ed., p. 946-947, Macmillan Publishing Co. (1975).
Polyethylene glycol ointment, U.S.P., PEG 300, NF, PEG 400, U.S.P., PEG 600, U.S.P., are all listed in the cited official compendia. PEG's are known as agents with the ability to provide mechanical occlusive protection from dermal irritants. Jellinik, Formulation and Function in Cosmetics, p. 322, Wiley--Interscience, New York (1970).
The use of a 50:50, by weight, mixture of PEG 400:PEG 4000 as a topical vehicle for a water-soluble active is well-known. Banker, et al., Modern Pharmaceutics, Marcel Dekker, P. 310 (1979).
Triacetin, (1,2,3-propanetriol triacetate), is a colorless, oily liquid which is known as a topical anti-fungal. The Merck Index, 9th Ed., p. 1232, Merck and Co. (1976). The "self-regulating" action of triacetin is known, i.e., it is known that at the neutral (or higher) pH of the affected skin, glycerol and free fatty acid (acetic acid) are rapidly liberated from triacetin as a result of the action of the esterase enzymes found abundantly in skin, serum, and fungi. The growth of the fungi is inhibited by the free fatty acid. See, entry for Enzactin.RTM. brand of triacetin, (Ayerst Laboratory Division of American Home Products), Physician's Desk Reference, 32nd Ed., p. 596 (1978).
Glycerol esters are known to be enzyme substrates, which, when acted upon by a hydrolyzing enzyme, will be hydrolyzed resulting in the release of free fatty acids.